ZIF‐8 Nanoparticles Evoke Pyroptosis for High‐Efficiency Cancer Immunotherapy

Although zeolitic imidazolate framework-8 (ZIF-8) has been applied in various tumor therapies, the intrinsic immunogenicity remains unclear. Here, we initiatively discover that ZIF-8 nanoparticles (NPs) can intrinsically induce pyroptosis by a caspase-1/gasdermin D (GSDMD)-dependent pathway. The pyroptotic cell death is accompanied by necrosis and immunogenic cell death (ICD) simultaneously for efficient in situ immunity initiation. Meanwhile, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), a mitochondrial depolarizing agent, is successfully loaded into ZIF-8 NPs and found to further enhance the pyroptosis process. Collectively, the obtained Pluronic F127-modified CCCP-incorporated ZIF-8 NPs (F127 ZIF-8CCCP NPs) activate antitumor immunity and reprogram immunosuppressive tumor microenvironment (TME), realizing high-efficiency tumor growth inhibition. This work will facilitate biomedicine applications of ZIF-8 and provide good inspiration for pyroptosis-induced cancer therapy.